In vivo blockade of Ca(+2)-dependent nitric oxide synthases impairs expressions of L-selectin and PECAM-1.
Interactions of leukocytes with endothelium play a role for the immune system modulated by endogenous agents, such as glucocorticoids and nitric oxide (NO). Glucocorticoids inhibit leukocyte-endothelial interactions whereas the role of NO is still controversial. In this study, the activity of Ca(+2)-dependent nitric oxide synthases was in vivo blocked in male Wistar rats by given l-NAME, 20mgkg(-1) for 14 days dissolved in drinking water and expression of adhesion molecules involved in leukocyte-endothelial interactions was investigated. Expressions of L-selectin and PECAM-1 in peripheral leukocytes and PECAM-1 in endothelial cells were reduced by l-NAME treatment. Only L-selectin expression was controlled at transcriptional levels. These effects were not dependent on endogenous glucocorticoids, as corticosterone levels were not altered in l-NAME-treated rats. Our results show that NO, produced at physiological levels, controls expression of constitutive adhesion molecules expressions in cell membranes by different mechanisms of action.
Hebeda
Cristina B
CB
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 0550-900, Av Prof. Lineu Prestes 580-BI13 B, SP, Brazil.
Teixeira
Simone A
SA
Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Muscará
Marcelo N
MN
Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Vinolo
Marco Antonio R
MAR
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Curi
Rui
R
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Mello
Suzana B V de
SBV
Rheumatology Division, Department of Internal Medicine, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
Farsky
Sandra H P
SHP
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 0550-900, Av Prof. Lineu Prestes 580-BI13 B, SP, Brazil. Electronic address: sfarsky@usp.br.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019041:L-Selectin / Q000096:biosynthesis* / Q000235:genetics; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019041:L-Selectin; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D003345:Corticosterone